PMCID string | Title string | Sentences string |
|---|---|---|
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The involvement of LTB4 in the recruitment of neutrophils in combination with other chemoattractants to inflamed joints was also shown (65, 66). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Our data suggest that the synergistic effect of LTB4 and CXCL12 is specific for CXCR4-induced chemotaxis since LTB4 has no effect on CXCR5-mediated migration of VAL-wt. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Nevertheless, we cannot fully exclude that CXCL12 scavenging by ACKR3 creates microgradients, which somehow modify CXCR4/CXCL12 signaling on ACKR3 negative cells. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Further studies are required to describe the molecular mechanism that supports the release of LTB4 upon ACKR3/CXCR4 stimulation. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Using a diffuse xenograft model we showed that spreading of VAL cells into tissues, such as brain, bone marrow and spleen, requires ACKR3 expression (32). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Given the poor prognosis of DLBCL patients with brain infiltrations (67, 68), understanding the underlying mechanism is of great clinical relevance. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Here we report that ACKR3 is required for DLBCL to escape from local tumors to move to draining lymph nodes resembling the spread of malignant cells from lumps or extra nodal sites. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Hence, targeting ACKR3-mediated tumor dissemination is appealing. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Our data showing the involvement of the LTB4/BLT1R axis in VAL cell migration, could open a way for the development of novel therapeutic approaches in the treatment of DLBCL, potentially in combination with inhibitors of ACKR3 (69–72). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | VAL and DOHH2 cells were cultured in RPMI-1640 supplemented with 10% heat-inactivated Fetal Bovine Serum (FBS), 1% Penicillin/Streptomycin (P/S), 1% GlutaMAX. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | 1% NEAA, 1% Sodium-Pyruvate and 50 µM β-mercaptoethanol all from Thermo Fisher. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Primary murine lymphatic endothelial cells (mLEC) were isolated from lymph nodes of C57BL/6 mice and cultured in αMEM (Thermo Fisher) supplemented with 10% heat-inactivated FBS, 1% P/S. Cells were cultured in humidified air at 37° C with 5% CO2. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Freshly harvested lymph nodes were harvested from C57BL/6 mice, and incubated in digestion mixture containing RPMI-1640, 0.25 mg/mL Liberase TL (Roche, Cat: 5401020001), 200 Kunits/mL DNAse I (Sigma-Aldrich, Cat: 10104159001) at 37° C for 1h with occasional shaking. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Single cell suspensions were strained using a 70 µm cell strainer (Corning), centrifuged and resuspended in αMEM. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells were plated on 6-well plates coated with 10 µg/mL PureCol (Collagen, Sigma-Aldrich) and human 10 µg/mL plasma Fibronectin (Sigma-Aldrich). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | After 3 hours non-adhering cells were removed. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | 5-7 days later, when >80% confluence was achieved, cells were detached using Accutase (Biological Industries). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Under these conditions blood endothelial cells die and the remaining cells are composed of fibroblastic reticular cells (FRCs) (~40%) and LECs. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | LECs were purified by staining with APC-conjugated anti-mouse CD31 (Biolegend, clone 390) and positively selected using anti-APC microbeads according to manufacturer’s instructions (Miltenyi Biotec). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | ACKR3 and the C-terminus deficient variant ACKR3-ΔC (6) were cloned into CDH-IF1-MCS-COP-GFP vector and nucleofected (Lonza) into CFP VAL-ko (32) giving rise to VAL-wt rescue and VAL-ACKR3-ΔC. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The transfected constructs expressed GFP after a T2A cleavage sequence, which was used for clonal selection by flow cytometry and single cell sorting (FACS-ARIA). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | CRISPR/Cas-9 ribonucleoproteins (crRNPs) targeting blt1r gene were delivered to VAL-wt cells by transfection with NEON nucleofector (Invitrogen, MA, USA) at 1’600 V, 10 ms, 3 pulses, using the provided buffer R. 10 cells were used with the 10-μl tip transfection. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The crRNAs (/AltR1/rCrArU rGrArG rUrCrU rArGrA rCrCrG rCrUrC rArCrG rUrUrU rUrArG rArGrC rUrArU rGrCrU/AltR2/”), tracrRNAs (IDT, USA) and HiFi Cas9 Nuclease V3 (IDT, USA) transfection was performed as indicated in the manufacturer’s instruction (IDT, USA). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Deletion of blt1r was confirmed by genomic sequencing of the locus. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | For flow cytometry cells were suspended in MACS buffer (phosphate buffered saline (PBS), 2% FBS, 2mM EDTA) and stained for 15 minutes on ice with the indicated antibodies. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | For chemokine uptake, 50 nM of fluorescently labelled chemokine (42, 73) was added to cells for 45 min at 37°C. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Mean fluorescence intensity (MFI) of the fluorophore were determined by flow cytometry (Fortessa or FACSCanto (BD) and FlowJo software. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Lymphoma cell migration was measured in transmigration assays using 5 µm transwell inserts. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | mLECs were seeded on polycarbonate inserts coated with 10 µg/mL fibronectin and 10 µg/mL collagen. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Monolayers of endothelial cells were grown by adding medium to the upper compartment, leaving the lower compartment empty. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | For LTB4-induced migration lymphoma cells were embedded in a collagen matrix formed by 1.6 mg/mL PureCol, 0.36% PBS supplemented with 0.36% FBS, 0.036% P/S, 1.5 µg/mL recombinant human ICAM-1/CD54 Fc chimera (R&D systems) at 4° C. To induce collagen polymerization the temperature was slowly raised over 45 min to 37°C. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Then medium was added on the upper compartment of the transwell inserts for 24 h before the experiment. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | When indicated, embedded cells were pretreated with 1 µM BIIL315 (OpnMe-Boehringer Ingelheim) for one hour at 37°C. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The medium of the upper compartment was then replaced with fresh medium containing 1 µM BIIL315, which was also present in the lower compartment during the experiment. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Lymphoma cells were pretreated with 10 µM AMD3100 (Sigma-Aldrich) for one hour at 37° C and transwell migration was performed in the presence of the same concentration of the inhibitor in the upper and lower compartment. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells were treated with 2 µg/mL pertussis toxin (PTX) (Sigma-Aldrich) for two hours at 37°C., |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | washed and added to inserts coated with endothelial cells without toxin. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Migration was stimulated with chemoattractants at the indicated concentrations in the lower compartment. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells were allowed to migrate to the lower chamber for 8 hours. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | After a brief centrifugation (1 min, 250 x g) of the inserts, cells were collected by centrifugation and resuspended in 100 µL of MACS buffer. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | For cell number determination cells were counted for 50 sec by flow cytometry. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells were resuspended at 10 cells mL in PBS and incubated for 30 minutes on ice. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells were centrifuged at 350g for 3 minutes, re-suspended at 10 cells mL in plain RPMI and incubated for 30 minutes at 37°C. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Secretion of LTB4 was stopped by centrifugation at 4° C (350g for 3 minutes) and supernatants collected. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | LTB4 ELISA was performed as indicated in the manufacturer’s instruction (Enzo Life Sciences). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Lymphoma cell migration in 3D chemotaxis were performed using µ-Slide Chemotaxis (Ibidi). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells were embedded in a collagen matrix as described above. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | To optimize and standardize the architecture of the collagen fibers we slowly induced polymerization by precooling and extending the warming rate from 4°C (liquid) to 37°C (solid) of the collagen matrix (74) (75). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The IBD chambers were loaded at 4°C and slowly warmed up to room temperature (20 min) before placing into a 37°C cell incubator. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Total warming time to 37°C was about 40 min. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The condition allows the formation of thin fibers with homogenous diameter, length and density and prevents the formation of fibers in hierarchical structures (74) (75). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | After polymerization complete medium (65 µL) was added on both side-reservoirs. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells embedded in the collagen matrix in the µ-Slide chamber were incubated in a humidified environment at 37°C and 5% CO2 for one day. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | After 24 hours 15 µL of 400 nM CXCL12 were added to one of the reservoirs and migration observed for 6 hours by time-lapse video microscopy (ImageXpress Molecular Devices) at 2 minutes or 20 seconds time intervals between frames. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The localized mouse xenograft model was described previously (32). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | 8–10-week-old mice were injected subcutaneously with 10 VAL or DOHH2 cells in PBS, or only PBS for control groups. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | All in vivo experiments were performed following the rules of the Swiss Federal Veterinary Office guidelines and authorized by the Animal Studies Committee of Cantonal Veterinary. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | A day before culling 50 µL of Evans Blue (2 µg/mL) were injected subcutaneously on the flank close to the xenograft do visualize lymphatic vessels. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Localized tumors and draining axillary lymph node were surgically removed and disintegrated with 150 µm Sefar Nitex filters and cells processed for flow cytometry analysis as described (76). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells of the disintegrated lymph node were resuspended in 150 µL of MACS buffer and analyzed by flow cytometry. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Tumors and lymph nodes were collected and fixed with a solution of 4% paraformaldehyde and washed with PBS, 1% FBS and 0.05% NaN3. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The organs were embedded in low melting agarose (Sigma-Aldrich) and 50-100 µm sections were prepared with a Leica VT1200S Vibratome. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Images were acquired with a confocal microscope (Leica SP5) and analyzed with Imaris software (Bitplane). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | For each condition, five biological replicates of cells were separately cultured, treated and sorted. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | DLBCL VAL cells were stained with 5 µg/mL anti-human ACKR3 (mAb 11G8). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | at 4°C for 15 min. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Cells were washed twice with MACS Buffer and sorted (5x10 cells) for ACKR3 positivity or negativity in 500 µL of RNA-later (Sigma-Aldrich). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | RNA-later lysates were centrifuged at 2500g x 5 minutes. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The Zymo column RNA Isolation kit was used for RNA extraction (Zymo). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Transcripts were processed for RNAseq with E7765L NEBNext Ultra II Directional RNA Library Prep, Sample Purification Beads and E7490L NEBNext Poly(A) mRNA Magnetic Isolation Module. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | Poly-A RNA sequencing was performed with Illumina NextSeq500. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | RNA quantification was performed using Salmon v1.4.0 with hg38 transcriptome reference (77). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The expression levels of the transcripts were then compared in the R package DESeq2 v1.28.0 (78). |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The datasets presented in this study can be found in online repositories. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The names of the repository/repositories and accession number(s) can be found here https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE169144. |
PMC9878562 | ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production | The animal study was reviewed and approved by Swiss Federal Veterinary Office guidelines and authorized by the Animal Studies Committee of Cantonal Veterinary. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | The treatment of B cell malignancies has dramatically changed with the introduction of immunotherapy, especially chimeric antigen receptor T (CAR-T) cell therapy. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | However, only limited efficacy is observed in acute myeloid leukaemia (AML). |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | In the study, We detected CD123 and CLL-1 expression on leukaemia cells from Relapsed/Refractory AML (R/R AML) patients. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | Then, we constructed anti-CD123 CAR and CLL-1 CAR with different co-stimulation domains (CD28 or 4-1BB) and detected their anti-AML effects. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | To increase the efficacy of CAR-T cell therapy, we tested different strategies, including application of combined checkpoint inhibitors and histone deacetylase inhibitors (HDACi) in vivo and in vitro. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | We found CD123 and CLL-1 were highly expressed on AML cells. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | The proportions of T cell subsets and NK cells involved in anti-tumour or anti-inflammation processes in AML patients significantly decreased when compared with healthy donors. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | Both CD123 CAR and CLL-1 CAR displayed specific anti-AML effects in vitro. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | To improve the lysis effects of CAR-T cells, we combined CAR-T cell therapy with different agents. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | PD-1/PD-L1 antibodies only slightly improved the potency of CAR-T cell therapy (CD123 CAR-T 60.92% ± 2.9087% vs. 65.43% ± 2.1893%, 60.92% ± 2.9087% vs. 67.43% ± 3.4973%; 37.37% ± 3.908% vs. 41.89% ± 5.1568%, 37.37% ± 3.908% vs. 42.84% ± 4.2635%). |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | However, one HDACi (valproic acid [VPA]) significantly improved CAR-T cell potency against AML cells (CLL-1 CAR-T 34.97% ± 0.3051% vs. 88.167% ± 1.5327%, p < 0.0001; CD123 CAR-T 26.87% ± 2.7010% vs. 82.56% ± 3.086%, p < 0.0001 in MV411; CLL-1 CAR-T 78.77% ± 1.2061% vs. 93.743% ± 1.2333%, p < 0.0001; CD123 CAR-T 64.10% ... |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | Combination therapy prolonged the overall survival of mice when compared with single CD123 CAR-T cell therapy (median survival: 180 days vs. unfollowed). |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | A possible mechanism is that activated CD8+T cells upregulate natural-killer group 2 member D (NKG2D), and VPA upregulates NKG2D ligand expression in AML cells, contributing to NKG2D-mediated cytotoxicity of CAR-T cells against tumour cells. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | In conclusion, CD123 and CLL-1 are promising targets for AML CAR-T cell therapy. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | A combination of VPA pre-treatment and CAR-T against AML exhibits synergic effects. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | In recent years, preclinical studies of chimeric antigen receptor T (CAR-T) to treat acute myeloid leukemia (AML) have yielded promising results. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | Several tumor antigens targeted to AML have been explored, including CD33, CD123, C-type lectin-like molecule-1 (CLL-1), CD44v6, and CD7.1–4 Among them, CD123 and CLL-1 remain the most promising targets for AML.2 5 However, the short persistence of CAR-T cells and immune escape may result in a relapse of AML. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | Natural-killer group 2 member D (NKG2D) is normally expressed in all natural killer (NK), NK T cells (NKT), CD8 T cells, and subsets of γδ T cells.6 NKG2D recognizes a family of major histocompatibility complex (MHC) I chain-related molecules A and B and a family of six UL16-binding proteins 1-6 (ULBP1–6), which are wi... |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | HDACi can influence tumor immunogenicity, the microenvironment, and the functional activity of specific immune cells. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | Moreover, HDACi was reported to upregulate NKG2DL in AML. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | Therefore, it is likely that a combination of CAR-T cell therapy with agents involved in T cell activation could be a novel potency to treat AML by activating T cells. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | In the present study, we constructed anti-CD123 CAR and CLL-1 CAR, which displayed specific anti-AML effects in vivo and in vitro. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | To improve the therapeutic effect and overcome immune escape, we tested the combined CAR-T cell therapy with HDACi and programmed cell death protein-1 (PD-1) or its ligand PD-L1 antibodies to treat AML. |
PMC10391797 | Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia | Interestingly, one HDACi, valproic acid (VPA), could significantly synergize with CAR-T cell therapy to improve antitumor activity. |
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